The object of our investigation is to determine the enzymic mechanisms involved in tissue degradation in human skin. We are also investigating the role of proteinases in inducing chemotactic and inflammatory events. We are isolating and characterizing the major proteinases of skin and we are evaluating their role in chemotaxis. We have isolated and purified three distinct proteinases in human skin. The smallest molecular weight proteinases have been extensively studied and their chemical characteristics and amino acid composition have been established. This proteinase has been found in human epithelium, human lymphocytes, and cell cultures of human fibroblasts. This neutral proteinase is enriched in the lysosomal mitochondrial fraction of human fibroblasts. Injection of the purified enzyme into rabbit skin induces polymorphonuclear leukocyte infiltration. Chemotaxis is dependent upon enzyme action since inhibition of the exzyme with diisopropyl fluorophosphate completely inhibits polymorph infiltration of the cutis. We are producing monospecific antiserum to these enzymes so that we will have a specific inhibitor. We also anticipate investigating the cellular localization of these enzymes by immunocytochemical techniques.